Osteopontin (hereinafter referred to as “OPN”) is an acidic and calcium-binding glycoprotein abundant in bone. The matured OPN is cleaved in vivo by thrombin to yield two fragments, i.e., the N-terminal fragment of OPN (hereinafter referred to as “OPN N-half”) and the C-terminal fragment (hereinafter referred to as “OPN C-half”). For example, human osteopontin (hereinafter referred to as “hOPN”) is cleaved at the C-terminal 168th arginine on the hOPN amino acid sequence to yield two fragments, hOPN N-half and hOPN C-half.
The above-mentioned OPN has a variety of physiologically and pathologically important functions, for example, cell adhesion, cell migration, tumorigenesis, immune response and inhibition of complement-mediated cytolysis, etc. These various functions are mediated by a variety of cell-surface receptors. It has been elucidated that the OPN N-half cleaved by thrombin exposes the SVVYGLR (SEQ ID NO: 2) sequence at the C-terminal, through which OPN binds itself to integrin α9 or α4.
The applicant of the present invention has so far investigated the in vivo function of OPN and gradually made clear the relation between the above OPN N-half and a variety of diseases. For example, in the International Patent Application (Patent Document 1) filed by the applicant, it has been reported that the ratio of OPN N-half to the total OPN is increased in patients suffering from rheumatism.
Though the relation between OPN N-half and diseases has gradually been elucidated, it was very important to measure accurately OPN N-half in order to further make its relation with other diseases clear. The 2K1 antibody reported by the applicant in the above-identified International Patent Application, however, also recognizes the OPN not cleaved by thrombin in addition to the C-terminal recognition site of OPN N-half; thus, it was hard to say that OPN N-half can be accurately measured depending on conditions.
From the fact that the above OPN N-half cleaved from OPN by thrombin exposes the SVVYGLR (SEQ ID NO: 2) sequence, through which OPN binds itself to integrin α9 or α4, it was necessary to provide an antibody which specifically binds to at least one part of the above-mentioned sequence in order to inhibit the binding effectively.
Patent Document: WO02/081522 internationally published pamphlet